Overall Project Summary The over-arching goal of the Healthy Aging and Senile Dementia (HASD) study is to determine the factors that signal the imminent development of symptomatic Alzheimer disease (AD) in cognitively normal older adults. In pursuing this goal, HASD also will examine whether these predictive factors differ between African Americans and non-Hispanic whites, are influenced by sleep, or might be offset by genetic variants that protect against developing symptomatic AD. Finally, HASD will evaluate a novel method of assessing cognitive performance in naturalistic settings via a smartphone application. To accomplish these goals, HASD will assess and follow a richly phenotyped cohort that includes both cognitively normal older adults (~75%) and those with early-stage symptomatic AD (~25%). The longitudinal assessment protocol includes standard and novel clinical and cognitive measures, a six-day in-home sleep study, magnetic structural imaging studies of the brain, positron emission tomography studies of the brain to reveal the cerebral hallmarks of AD, amyloid-beta plaques and tau deposition, and examination of blood for genetic studies and of cerebrospinal fluid for levels of amyloid-beta and tau. Five Cores (Administration, Clinical, Biostatistics, Neuropathology [includes the Biofluids Laboratory], and Imaging) will support four Projects that carry out the scientific aims of HASD: Project 1: ?Characterization of Molecular Biomarker Profiles of AD throughout its Pathobiological Continuum? Project 2: ?Sleep and Orexin: Potential Markers of Progression from Preclinical to Mildly Symptomatic Alzheimer Disease? Project 3: ?Dissecting the Genetic Architecture of Resilience? Project 4: ?Smartphone-Based `Burst' Cognitive Assessments?